In this paper published in Nature Communications, researchers from ENS de Lyon and École Polytechnique Fédérale de Lausanne show the potential of metal analysis in living samples. By combining highly accurate metal quantification with biological and computational study, they establish that the distribution of metals in the body evolves with age in a highly reproducible way, and that metal fluctuations are associated with the metabolic health of mice.

Organic elements make up 99% of an organism but without the remaining inorganic bioessential elements, termed the metallome, no life could be possible. The metallome is involved in all aspects of life, including charge balance and electrolytic activity, structure and conformation, signaling, acid-base buffering, electron and chemical group transfer, redox catalysis energy storage and biomineralization. Here, we report the evolution with age of the metallome and copper and zinc isotope compositions in five mouse organs. The aging metallome shows a conserved and reproducible fingerprint. By analyzing the metallome in tandem with the phenome, metabolome and proteome, we show networks of interactions that are organ-specific, age-dependent, isotopically-typified and that are associated with a wealth of clinical and molecular traits. We report that the copper isotope composition in liver is age-dependent, extending the existence of aging isotopic clocks beyond bulk organic elements. Furthermore, iron concentration and copper isotope composition relate to predictors of metabolic health, such as body fat percentage and maximum running capacity at the physiological level, and adipogenesis and OXPHOS at the biochemical level. Our results shed light on the metallome as an overlooked omic layer and open perspectives for potentially modulating cellular processes using careful and selective metallome manipulation.

Reference: The mouse metallomic landscape of aging and metabolism. Morel JD, Sauzéat L, Goeminne LJE, Jha P, Williams E, Houtkooper RH, Aebersold R, Auwerx J, Balter V. Nat Commun. February 1^st, 2022.
doi: 10.1038/s41467-022-28060-x